Whole blood is made up of various cellular components such as red blood cells, white blood cells and platelets suspended in its liquid component, plasma. Whole blood can be separated into its constituent components (cellular or liquid), and the desired separated component can be administered to a patient in need of that particular component. For example, platelets can be removed from the whole blood of a healthy donor, collected, and later administered to a cancer patient whose ability to “make” platelets has been compromised by chemotherapy or radiation treatment.
White blood cells, sometimes referred to as leukocytes, are nucleated cells that play an important role in the human immune system. White blood cells protect the body's cells and tissue from foreign agents, infections and the like.
Leukocytes can be divided into three (3) groups, namely, granulocytes, monocytes and lymphocytes. (Granulocytes may further be subdivided into neutrophils, eosinophils and basophils.) Monocytes and lymphocytes are sometimes also referred to as mononuclear cells (MNC) because of their single lobed cell nucleus.
While white blood cells have routinely been separated from whole blood, their use as a component for later administration to a patient has not been as widely practiced when compared to other blood components such as red blood cells and platelets. However, recent advances in the medical community's understanding of the relationship between the immune system and the treatment of disease, such as certain cancers, CTCL and other disorders has focused more attention on the collection and use of white blood cells. White blood cells and, more specifically, mononuclear cells are increasingly being considered for use in therapeutic treatments of patients suffering from disease. White blood cells that have been separated as part of a whole blood separation process are, with greater frequency, being collected and later cultured or otherwise activated into cellular agents for use in the treatment of certain diseases.
Inasmuch as white blood cells typically only have a limited shelf life, (when kept at room temperature) they must be administered or otherwise used or cryopreserved soon after their collection. When cells are kept outside the body, they begin undergoing apoptosis, a form of cell death. However, use within 24 hours often proves to be logistically impractical, particularly where the white blood cells may have to be delivered to a different location or may have to be subjected to a culturing, treating or other processing step. Thus, white blood cells are often stored in a storage medium that helps maintain the viability of the white blood cells. Currently, the storage medium RPMI1640 is widely used in the storage (and culturing) of white blood cells. RPMI1640 is a complex storage medium that has been developed for culturing leukocytes and often requires some supplementation with human serum. In addition to its inorganic components, RPMI1640 further includes approximately 20 amino acids and 12 vitamins. As such, white blood cells stored in RPMI1640 cannot be readily transfused, but must typically be washed to remove the storage medium from the white blood cell product.
Storage media for the preservation of blood cells, blood fragments or other blood components are known. For example, synthetic media for the storage of platelets are disclosed in U.S. Pat. Nos. 5,569,579 (Murphy) and 5,908,742 (Lin et al.), which are incorporated herein by reference. InterSol®, a commercially available platelet storage medium is generally described in U.S. Pat. No. 5,908,742, the contents of which are incorporated by reference herein in its entirety. InterSol® contains sodium citrate, sodium acetate, sodium phosphate and adjusted to iso-osmolarity with sodium chloride.
Further examples of media useful in the storage of blood components, such as platelets, are described in U.S. Patent Application Publication No. US2009/0191537A1, filed Dec. 18, 2008, the contents of which are incorporated herein by reference and International Patent Application Serial No. PCT/US2012/32551, filed Apr. 6, 2012, the contents of which are likewise incorporated herein by reference. Storage media for red blood cells are described in U.S. Patent Application Publication No. US2011/0117647, the contents of which are also incorporated herein by reference. The solutions described above are typically readily transfusible to the patient.
While the solutions described above have worked satisfactorily for platelets and other blood components, synthetic solutions suitable for storing white blood cells and that maintain white blood cell viability and are readily transfusible to a patient are not widely available.
Thus, it would be desirable to provide a white blood cell product wherein the viability of the white blood cells is maintained in excess of 24 hours, so that the white blood cells can be used for subsequent administration to a patient.
In addition, it would be desirable to provide a medium that can be used for the storage of white blood cells and that can be readily transfused to a patient. In other words, it would be desirable to provide a readily transfusible white blood cell product (i.e., cells and medium).
Furthermore, it would be desirable to provide a storage solution or solution or medium that can be used to wash white blood cells, to remove any undesired agents or components of a storage medium such as those used in the culturing of white blood cells.
In addition, it would be desirable to provide a storage medium or solution that can itself be used as a culture medium or as part of a culture medium in combination with certain culturing components, such as human serum.
White blood cell products and the storage solutions and media used in such white blood cell products are described in greater detail below.